Effect of anti‐Notch 1 neutralizing antibody on the activity of human and mouse osteoclast progenitors stimulated by Notch‐ligands DLL1 and JAG1 (CROSBI ID 708212)
Prilog sa skupa u časopisu | sažetak izlaganja sa skupa | međunarodna recenzija
Podaci o odgovornosti
Filipović, Maša ; Šućur, Alan ; Flegar, Darja ; Jajić, Zrinka ; Ikić Matijašević, Marina ; Šisl, Dino ; Kelava, Tomislav ; Lukač, Nina ; Kovačić, Nataša ; Priselac, Sara ; Zrinski Petrović, Katerina ; Katavić, Vedran ; Grčević, Danka
engleski
Effect of anti‐Notch 1 neutralizing antibody on the activity of human and mouse osteoclast progenitors stimulated by Notch‐ligands DLL1 and JAG1
Bone loss associated with rheumatoid arthritis (RA) is caused by enhanced osteoclast differentiation and function. We aimed to determine the Notch receptor profile on human and mouse osteoclast progenitors (OCP) and the effect of Notch receptor signaling inhibition on OCP activity in murine collagen‐induced arthritis (CIA) and human RA samples. Peripheral blood was collected from RA patients. Periarticular bone marrow (PBM) and spleen (SPL) were harvested from mice with CIA, additionally treated by i.p. injections of anti‐Notch 1 neutralizing antibodies (1 mg/kg). FACS sorted OCPs were stimulated by osteoclastogenic factors (M‐CSF/RANKL), in Jagged (JAG)1 or Delta‐like (DLL)1 coated wells, with or without anti‐ Notch 1 neutralizing antibodies. The research was approved by the Ethics Committee. Both mouse (CD45+CD11blo/+CD115+CCR2+ or CCR2lo) and human (CD45+CD11b+CD14+CCR2+) OCPs express Notch receptors, with Notch 1 and 2 being the most abundantly detected. In vitro stimulation with DLL1 significantly increased, while stimulation with JAG1 significantly decreased osteoclastogenesis. The addition of anti‐Notch 1 to ligand‐stimulated OCPs resulted in an increased number of TRAP+ osteoclasts, partially reversing JAG1 inhibition. Both PBM and SPL OCPs from mice in vivo treated with anti‐Notch 1 produced a higher number of TRAP+ osteoclasts, with increased expression of osteoclast differentiation genes. Our results confirm that Notch signaling regulates osteoclast differentiation, with DLL1 exhibiting a stimulatory, and JAG1 a suppressive role. Anti‐ Notch 1 neutralizing antibodies partially reversed suppression by JAG1, proposing Notch 1/JAG1 pathway as a possible therapeutic target for the regulation of osteoclast activity in arthritis.
animal models ; autoimmunity ; cell signalling ; myeloid cells ; rheumatoid arthritis
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Podaci o prilogu
388-388.
2021.
nije evidentirano
objavljeno
10.1002/eji.202170200
Podaci o matičnoj publikaciji
European journal of immunology
0014-2980
1521-4141
Podaci o skupu
6th European congress of immunology (ECI 2021)
poster
01.09.2021-04.09.2021
online
Povezanost rada
Temeljne medicinske znanosti